The successful treatment of wounds to regenerate healthy and functional skin remains a huge challenge due to the skin's multilayered structure, the presence of multiple different cell types organized within the extracellular matrix, and different biochemical pathways present in different wound types (e.g., acute wounds, chronic wounds, burns, etc.). An aging population and its requisite medical interventions, the continuing rise in diabetes and obesity, and an increase in the occurrence of traumatic wounds all translate to large increases in skin wounds needing treatment.
Particularly problematic are chronic non-healing wounds, which are estimated to affect approximately 2% of the general U.S. population. Patients with these hardest-to-heal wounds include those with diabetes, sickle cell ulcers, vasculitis, and scleroderma, as well as obese individuals. The cost of caring for chronic wounds in the U.S. alone is reported to exceed $50 billion annually.
While wound healing technology has grown rapidly, offering new products applicable for both acute (including both traumatic and surgical wounds) and chronic wound management, need for further improvement exists. For example, it is estimated that among the 2 million people diagnosed yearly with pressure ulcers, 900,000 remain non-healing after initial treatment, and reports indicate that of 800,000 diabetic foot ulcers treated in the U.S. yearly, 30% don't respond to common treatments.
Currently marketed drugs for use in severe wound treatment include Regranex® (Becarplermin), a genetically engineered recombinant platelet-derived growth factor, silver-based products such as silver sulfadiazine and Silvadene®, and wound dressings loaded with active ingredients such as silver, bismuth, chlorhexidine, bacitracin, hydrocortisone, or lidocaine. Growth factors such as transforming growth factor beta and fibroblast growth factors as well as Living Skin Equivalents (LSEs) are another class of advanced wound care products. Other products include different classes of keratolytics, antiseptics, sulfa-antibiotics, and collagen-specific enzymes. Many currently available wound healing medications are based on growth factors, cytokines, chemokines, collagen or hyaluronic acid. There are disadvantages associated with such agents due to side effects including inflammatory response and undesired stimulation of other cell types. There are also reported side effects for silver-containing products including bacterial resistance, cytotoxic effects, and hepatic or renal toxicity.
Such issues call for alternative wound healing agents that can provide more effective and rapid wound treatments with fewer side effects. Safer compounds that can promote the epithelialization and vascular formation in both acute and chronic wounds as well as other applications calling for similar activities would be of great benefit.
Natural products provide a historically successful source of medicinally active compounds and have the potential to provide targeted healing responses while limiting the undesirable side effects associated with many currently utilized treatments. Wound therapies based on natural compounds such as plant extracts and natural active components offer viable alternatives to synthetic pharmaceuticals, enhancing access to healthcare, and overcoming limitations associated with synthetic products and therapies, including high costs, long manufacturing times, and increased bacterial resistance.